RNAi-Based Strategies for Cyclooxygenase-2 Inhibition in Cancer

Figure 3

The different strategies for COX-2 blockade. (a) COX-2 selective NSAIDs (e.g., celecoxib, rofecoxib, etoricoxib) represent to date the only drugs marketed for COX-2 selective inhibition, even if rofecoxib has been withdrawn due to its toxicity; (b) inhibitors of transcriptional factors expression and/or activity (e.g., C/EBP𝛽 transactivator) may block COX-2 overexpression associated to inflammation or cancer; (c) anti-COX-2 siRNAs (siCOX-2) or miRNAs (e.g., miR-101) with structural modifications that improve their stability may block COX-2 expression after intravenous administration; (d) polymer- or lipid-based delivery systems protect siRNAs or miRNA from the extracellular environment and, modifying their shell, a more selective cellular targeting can be obtained; (e) nonpathogenic bacteria (E. coli) can be engineered in order to invade target cells and induce RNAi against COX-2 (transkingdom RNAi, tkRNAi) by releasing DNA plasmids that express siCOX-2 or miR-101 precursors; (f) anti-COX-2 shRNA (shCOX-2) or pre-miRNA expression cassettes can be transduced into target cells genome by the use of recombinant retroviruses, allowing a stable COX-2 silencing into mammalian cells.